[en] Purpose: A new device has been developed with the goal of making breast-conserving therapy more widely available, by making breast brachytherapy as monotherapy simpler and more accurate. This is the first published report on the dosimetric characteristics of this device. Methods and Materials: The experience of a single institution participating in a multi-institutional trial is reported. Twelve patients were enrolled, of whom 8 were treated. Computed tomography scans of all 12 patients were obtained before initiation of treatment. A commercial three-dimensional planning system was used for retrospective detailed analysis of dosimetry, including dose-volume histograms and, in selected patients, skin dose distributions. These data were compared to those of a similar group of patients, analyzed previously, that was treated with interstitial high-dose-rate brachytherapy. Results: Compared with interstitial brachytherapy, the MammoSite device resulted in a treatment dose that was less uniform, with a mean dose homogeneity index of 0.77 vs. 0.93. Coverage and reproducibility were improved, with a mean D90 (minimum dose to 90% of target volume) of 90.0% of prescribed dose (SD 0.5, range: 89.2-90.8%) vs. 69.8% (SD 7.3, range: 61.1-83.5%) for interstitial brachytherapy. Conclusions: Reproducible placement was easily achieved in this very early experience, indicating a much smaller 'learning curve' than for interstitial brachytherapy. Because skin doses can be increased with the use of this device, caution is indicated, although simple maneuvers can significantly reduce skin dose

[en] Purpose: A direct approach to the question of whether prostate tumors have an atypically high sensitivity to fractionation (low α/β ratio), more typical of the surrounding late-responding normal tissue. Methods and Materials: Earlier estimates of α/β for prostate cancer have relied on comparing results from external beam radiotherapy (EBRT) and brachytherapy, an approach with significant pitfalls due to the many differences between the treatments. To circumvent this, we analyze recent data from a single EBRT + high-dose-rate (HDR) brachytherapy protocol, in which the brachytherapy was given in either 2 or 3 implants, and at various doses. For the analysis, standard models of tumor cure based on Poisson statistics were used in conjunction with the linear-quadratic formalism. Biochemical control at 3 years was the clinical endpoint. Patients were matched between the 3 HDR vs. 2 HDR implants by clinical stage, pretreatment prostate-specific antigen (PSA), Gleason score, length of follow-up, and age. Results: The estimated value of α/β from the current analysis of 1.2 Gy (95% CI: 0.03, 4.1 Gy) is consistent with previous estimates for prostate tumor control. This α/β value is considerably less than typical values for tumors (≥8 Gy), and more comparable to values in surrounding late-responding normal tissues. Conclusions: This analysis provides strong supporting evidence that α/β values for prostate tumor control are atypically low, as indicated by previous analyses and radiobiological considerations. If true, hypofractionation or HDR regimens for prostate radiotherapy (with appropriate doses) should produce tumor control and late sequelae that are at least as good or even better than currently achieved, with the added possibility that early sequelae may be reduced

[en] Purpose: To present our clinical experience using intensity-modulated radiation therapy (IMRT) to improve dose uniformity and treatment efficacy in patients with early-stage breast cancer treated with breast-conserving therapy. Methods and Materials: A total of 281 patients with Stage 0, I, and II breast cancer treated with breast-conserving therapy received whole breast RT after lumpectomy using our static, multileaf collimator (sMLC) IMRT technique. The technical and practical aspects of implementing this technique on a large scale in the clinic were analyzed. The clinical outcome of patients treated with this technique was also reviewed. Results: The median time required for three-dimensional alignment of the tangential fields and dosimetric IMRT planning was 40 and 45 min, respectively. The median number of sMLC segments required per patient to meet the predefined dose-volume constraints was 6 (range 3-12). The median percentage of the treatment given with open fields (no sMLC segments) was 83% (range 38-96%), and the median treatment time was <10 min. The median volume of breast receiving 105% of the prescribed dose was 11% (range 0-67.6%). The median breast volume receiving 110% of the prescribed dose was 0% (range 0-39%), and the median breast volume receiving 115% of the prescribed dose was also 0%. A total of 157 patients (56%) experienced Radiation Therapy Oncology Group Grade 0 or I acute skin toxicity; 102 patients (43%) developed Grade II acute skin toxicity and only 3 (1%) experienced Grade III toxicity. The cosmetic results at 12 months (95 patients analyzable) were rated as excellent/good in 94 patients (99%). No skin telengiectasias, significant fibrosis, or persistent breast pain was noted. Conclusion: The use of intensity modulation with our sMLC technique for tangential whole breast RT is an efficient method for achieving a uniform and standardized dose throughout the whole breast. Strict dose-volume constraints can be readily achieved resulting in both uniform coverage of breast tissue and a potential reduction in acute and chronic toxicities. Because the median number of sMLC segments required per patient is only 6, the treatment time is equivalent to conventional wedged-tangent treatment techniques. As a result, widespread implementation of this technology can be achieved with minimal imposition on clinic resources and time constraints

[en] Purpose: The clinical significance of postradiotherapy (RT) prostate biopsy characteristics is not well understood relative to the known prognostic factors. We performed a detailed pathologic review of posttreatment biopsy specimens in an attempt to clarify their relationship with clinical outcome and radiation dose. Methods and Materials: Between 1991 and 1998, 78 patients with locally advanced prostate cancer were prospectively treated with external beam RT in combination with high-dose-rate brachytherapy at William Beaumont Hospital and had post-RT biopsy material available for a complete pathologic review. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen level ≥10.0 ng/mL, Gleason score ≥7, or clinical Stage T2b-T3cN0M0. Pelvic external beam RT (46.0 Gy) was supplemented with three (1991-1995) or two (1995-1998) ultrasound-guided transperineal interstitial ¹⁹²Ir high-dose-rate implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Post-RT prostate biopsies were performed per protocol at a median interval of 1.5 years after RT. All pre- and post-RT biopsy specimen slides from each case were reviewed by a single pathologist (N.S.G.). The presence and amount of residual cancer, most common RT-effect score, and least amount RT-effect score were analyzed. The median follow-up was 5.7 years. Biochemical failure was defined as three consecutive prostate-specific antigen rises. Results: Forty patients (51%) had residual cancer in the post-RT biopsies. The 7-year biochemical control rate was 79% for patients with negative biopsies vs. 62% for those with positive biopsies with marked RT damage vs. 33% for those with positive biopsies with no or minimal RT damage. A greater percentage of positive pre-RT biopsy cores (p=0.01), lower total RT dose (p=0.001), lower dose per implant (p=0.001), and greater percentage of positive post-RT biopsy cores (p=0.01) were each associated with biochemical failure (Cox regression, univariate analysis). For patients with <25% positive post-RT biopsy cores, the 7-year biochemical control rate was 81% vs. a 62% biochemical control rate for those with 25-49% positive cores and only 32% for those with ≥50% positive cores (p=0.01). On Cox multiple regression analysis, only the percentage of positive pre-RT biopsy cores and RT dose remained significantly associated with biochemical failure. Of all the factors analyzed, only the pretreatment cancer volume and lower RT dose were significantly associated with residual cancer and/or residual cancer with no or minimal RT damage. A greater percentage of positive pre-RT biopsy cores was associated with both a positive post-RT biopsy (p=0.08) and a greater percentage of positive post-RT biopsy cores (p=0.04). A lower total RT dose was associated with both a positive post-RT biopsy (p=0.08) and a greater percentage of positive post-RT biopsy cores (p=0.02). For patients who received <80 Gy (equivalent in 2-Gy fractions), 73% had positive post-RT biopsies vs. a 56% biopsy positivity rate for those who received 84-90 Gy and only 39% for those who received ≥92 Gy (p=0.07). Conclusion: Patients with positive post-RT biopsies are more likely to experience biochemical failure, especially when the RT damage is minimal. Patients who have a larger pretreatment tumor volume or receive a lower RT dose are more likely to demonstrate post-RT biopsy positivity and biochemical failure

[en] Purpose: To evaluate the long-term results of treatment using adjuvant whole abdominal irradiation (WAPI) with a pelvic/vaginal boost in patients with Stage I-III endometrial carcinoma at high risk of intra-abdominopelvic recurrence, including clear cell (CC) and serous-papillary (SP) histologic features. Methods and Materials: In a prospective nonrandomized trial, 119 patients were treated with adjuvant WAPI between November 1981 and April 2000. All patients were analyzed, including those who did not complete therapy. The mean age at diagnosis was 66 years (range 39-88). Thirty-eight patients (32%) had 1989 FIGO Stage I-II disease and 81 (68%) had Stage III. The pathologic features included the following: 64 (54%) with deep myometrial invasion, 48 (40%) with positive peritoneal cytologic findings, 69 (58%) with high-grade lesions, 21 (18%) with positive pelvic/para-aortic lymph nodes, and 44 (37%) with SP or CC histologic findings. Results: The mean follow-up was 5.8 years (range 0.2-14.7). For the entire group, the 5- and 10-year cause-specific survival (CSS) rate was 75% and 69% and the disease-free survival (DFS) rate was 58% and 48%, respectively. When stratified by histologic features, the 5- and 10-year CSS rate for adenocarcinoma was 76% and 71%, and for serous papillary/CC subtypes, it was 74% and 63%, respectively (p=0.917). The 5- and 10-year DFS rate for adenocarcinoma was 60% and 50% and was 54% and 37% serous papillary/CC subtypes, respectively (p=0.498). For surgical Stage I-II, the 5-year CSS rate was 82% for adenocarcinoma and 87% for SP/CC features (p=0.480). For Stage III, it was 75% and 57%, respectively (p=0.129). Thirty-seven patients had a relapse, with the first site of failure the abdomen/pelvis in 14 (38%), lung in 8 (22%), extraabdominal lymph nodes in 7 (19%), vagina in 6 (16%), and other in 2 (5%). When stratified by histologic variant, 32% of patients with adenocarcinoma and 30% with the SP/CC subtype developed recurrent disease. Most failures for either histologic group occurred within the abdominopelvic region. However, one-third of the adenocarcinoma recurrences were in the lung. Multivariate regression analysis (age, surgical stage, grade, myometrial invasion, histologic type, lymph node status, and peritoneal cytology) demonstrated age (p=0.019) and surgical stage (p=0.036) to be of prognostic significance for CSS; age (p=0.036) was the only significant prognostic factor for DFS. Grade 1-2 gastrointestinal and hematologic acute toxicities were common. Asymptomatic bibasilar scarring on chest X-ray and mild elevation of liver enzymes were seen in almost 50% of the patients. Even though chronic toxicities were less frequent, 12% developed Grade 3-4 gastrointestinal and 2% Grade 3 renal toxicities. Conclusion: Adjuvant WAPI is very effective treatment with excellent 10-year results for Stage I-III endometrial carcinoma with risk factors for intra-abdominopelvic recurrence, including SP or CC histologic variants, deep myometrial invasion, high grade, nodal involvement, and positive peritoneal cytology. The low long-term complication rate with high CSS rate makes WAPI the treatment of choice for these patients with significant comorbidities

[en] Purpose: We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI). Methods and Materials: A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. Results: Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p < 0.001) when compared with patients diagnosed with IDC. The 5-year rate of LR was 0% for the ILC cohort and 2.5% for the IDC cohort (p = 0.59). No differences were seen in the rates of RR (0% vs. 0.7%, p = 0.80), distant metastases (0% vs. 3.5%, p = 0.54), DFS (100% vs. 94%, p = 0.43), CSS (100% vs. 97%, p = 0.59), or OS (92% vs. 89%, p = 0.88) between the ILC and IDC patients, respectively. Additionally, when node-positive patients were excluded from the IDC cohort, no differences in the rates of LR (0% vs. 2.2%, p = 0.62), RR (0% vs. 0%), DFS (100% vs. 95%, p = 0.46), CSS (100% vs. 98%, p = 0.63), or OS (92% vs. 89%, p = 0.91) were noted between the ILC and IDC patients. Conclusion: Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology.

[en] Purpose: This prospective study examines the use of three-dimensional conformal external beam radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Four-year data on efficacy, cosmesis, and toxicity are presented. Methods: Patients with Stage O, I, or II breast cancer with lesions ≤3 cm, negative margins, and negative nodes were eligible. The 3D-CRT delivered was 38.5 Gy in 3.85 Gy/fraction. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Disease-free, overall, and cancer-specific survival (DFS, OS, CSS) were recorded. The National Cancer Institute Common Terminology Criteria for Adverse Events (version 3) toxicity scale was used to grade acute and late toxicities. Results: Ninety-four patients are evaluable for efficacy. Median patient age was 62 years with the following characteristics: 68% tumor size <1 cm, 72% invasive ductal histology, 77% estrogen receptor (ER) (+), 88% postmenopausal; 88% no chemotherapy and 44% with no hormone therapy. Median follow-up was 4.2 years (range, 1.3-8.3). Four-year estimates of efficacy were IBF: 1.1% (one local recurrence); INF: 0%; CBF: 1.1%; DF: 3.9%; DFS: 95%; OS: 97%; and CSS: 99%. Four (4%) Grade 3 toxicities (one transient breast pain and three fibrosis) were observed. Cosmesis was rated good/excellent in 89% of patients at 4 years. Conclusions: Four-year efficacy, cosmesis, and toxicity using 3D-CRT to deliver APBI appear comparable to other experiences with similar follow-up. However, additional patients, further follow-up, and mature Phase III data are needed to evaluate thoroughly the extent of application, limitations, and complete value of this particular form of APBI.

[en] Purpose: Initial Phase I/II results using balloon brachytherapy to deliver accelerated partial breast irradiation (APBI) in 2 days in patients with early-stage breast cancer are presented. Materials and Methods: Between March 2004 and August 2007, 45 patients received adjuvant radiation therapy after lumpectomy with balloon brachytherapy in a Phase I/II trial delivering 2800 cGy in four fractions of 700 cGy. Toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria for Adverse Events v3.0 scale and cosmesis was documented at ≥6 months. Results: The median age was 66 years (range, 48-83) and median skin spacing was 12 mm (range, 8-24). The median follow-up was 11.4 months (5.4-48 months) with 21 patients (47%) followed ≥1 year, 11 (24%) ≥2 years, and 7 (16%) ≥3 years. At <6 months (n = 45), Grade II toxicity rates were 9% radiation dermatitis, 13% breast pain, 2% edema, and 2% hyperpigmentation. Grade III breast pain was reported in 13% (n = 6). At ≥6 months (n = 43), Grade II toxicity rates were: 2% radiation dermatitis, 2% induration, and 2% hypopigmentation. Grade III breast pain was reported in 2%. Infection was 13% (n = 6) at <6 months and 5% (n = 2) at ≥6 months. Persistent seroma ≥6 months was 30% (n = 13). Fat necrosis developed in 4 cases (2 symptomatic). Rib fractures were seen in 4% (n = 2). Cosmesis was good/excellent in 96% of cases. Conclusions: Treatment with balloon brachytherapy using a 2-day dose schedule resulted acceptable rates of Grade II/III chronic toxicity rates and similar cosmetic results observed with a standard 5-day accelerated partial breast irradiation schedule.

[en] Purpose: We applied the American Society of Therapeutic Radiology and Oncology (ASTRO) Consensus Panel (CP) guidelines for the use of accelerated partial breast irradiation (APBI) to patients treated with this technique to determine the ability of the guidelines to differentiate patients with significantly different clinical outcomes. Methods and Materials: A total of 199 patients treated with APBI and 199 with whole-breast irradiation (WBI) (matched for tumor size, nodal status, age, margins, receptor status, and tamoxifen use) were stratified into the three ASTRO CP levels of suitability ('suitable,' 'cautionary,' and 'unsuitable') to assess rates of ipsilateral breast tumor recurrence (IBTR), regional nodal failure, distant metastases, disease-free survival, cause-specific survival, and overall survival based on CP category. Median follow-up was 11.1 years. Results: Analysis of the APBI and WBI patient groups, either separately or together (n = 398), did not demonstrate statistically significant differences in 10-year actuarial rates of IBTR when stratified by the three ASTRO groups. Regional nodal failure and distant metastasis were generally progressively worse when comparing the suitable to cautionary to unsuitable CP groups. However, when analyzing multiple clinical, pathologic, or treatment-related variables, only patient age was associated with IBTR using WBI (p = 0.002). Conclusions: The ASTRO CP suitable group predicted for a low risk of IBTR; however, the cautionary and unsuitable groups had an equally low risk of IBTR, supporting the need for continued refinement of patient selection criteria as additional outcome data become available and for the continued accrual of patients to Phase III trials.

[en] Purpose: To examine clinical outcomes of accelerated partial-breast irradiation (APBI) stratified by the number of American Society for Radiation Oncology consensus statement cautionary/unsuitable risk factors (RFs) present. Methods and Materials: A total of 692 patients were treated with APBI at a single institution between April 1993 and January 2012 using interstitial (n=195), balloon (n=292), and 3-dimensional conformal radiation therapy (n=205) techniques. Clinical outcomes were evaluated by risk group and number of RFs. Results: Median follow-up was 5.2 years (range, 0-18.3 years). Most patients were classified as suitable (n=240, 34%) or cautionary (n=343, 50%) risk, whereas 16% (n=109) were unsuitable. In patients with increasing total RFs (1 RF, 2 RF, 3+ RF), higher rates of grade 3 histology (10% vs 18% vs 32%, P<.001), estrogen receptor negativity (0 vs 12% vs 29%, P<.001), close/positive margins (0 vs 6% vs 17%, P<.001), and use of adjuvant chemotherapy (3% vs 12% vs 33%, P<.001) were noted. When pooling cautionary and unsuitable patients, increased ipsilateral breast tumor recurrence/regional recurrence was most notable for patients with 3 or more combined RFs versus 2 or fewer combined RFs (P<.001). Conclusions: Patients with 3 or more cautionary or unsuitable RFs may be at risk for higher local, regional, and distant recurrence after breast-conserving therapy using APBI. Patients with 2 or fewer total RFs have 98% locoregional control at 5 years. Inclusion of total number of RFs in future risk stratification schemes for APBI may be warranted